Pertuzumab Plus Trastuzumab in Patients With Lung Cancer With <i>ERBB2</i> Mutation or Amplification: Results From the Targeted Agent and Profiling Utilization Registry Study.

Abstract

The Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with lung cancer and <i>ERBB2</i> mutation or amplification treated with pertuzumab plus trastuzumab (P + T) are reported. Eligible patients had advanced lung cancer of any histology, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with <i>ERBB2</i> mutation or amplification. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) per RECIST v. 1.1 or stable disease (SD) of at least 16 weeks duration (SD16+). Secondary end points included safety, duration of response, duration of SD, progression-free survival, and overall survival. Twenty-eight patients with lung cancer (27 non-small-cell, 1 small-cell) and <i>ERBB2</i> mutation (n = 15), <i>ERBB2</i> amplification (n = 12), or both (n = 1) were enrolled from November 2016 to July 2020. All patients were evaluable for efficacy and toxicity. Three patients with partial response (two <i>ERBB2</i> mutation; one both mutation and amplification) and seven patients with SD16+ (five <i>ERBB2</i> mutation; two amplification) were observed for a DC rate of 37% (95% CI, 21 to 50; <i>P</i> = .005) and OR rate of 11% (95% CI, 2 to 28). Five patients had one or more grade 3 or 4 adverse or serious adverse events at least possibly related to P + T. Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non-small-cell lung cancer and <i>ERBB2</i> mutation or amplification, particularly those with <i>ERBB2</i> exon 20 insertion mutations.